PMID- 34699032
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20231106
IS  - 1179-1888 (Electronic)
IS  - 1175-0561 (Linking)
VI  - 23
IP  - 2
DP  - 2022 Mar
TI  - Skin Toxicities with Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: 
      Signals from Disproportionality Analysis of the FDA Adverse Event Reporting 
      System.
PG  - 247-255
LID - 10.1007/s40257-021-00645-0 [doi]
AB  - BACKGROUND: Cyclin-dependent kinase (CDK)-4/6 inhibitors have been associated 
      with dermatologic reactions, especially alopecia, in pivotal trials. OBJECTIVE: 
      We aimed to comprehensively describe skin toxicities with CDK4/6 inhibitors 
      reported in the real world through the US FDA Adverse Event Reporting System 
      (FAERS). METHODS: Cutaneous adverse events (AEs) were characterized in terms of 
      spectrum and clinical features, including seriousness (with fatality proportion), 
      latency, and discontinuation. Disproportionality analyses were performed through 
      the reporting odds ratio (ROR) and 95% confidence interval (CI) by comparing 
      CDK4/6 inhibitors with other anticancer drugs used in breast cancer. RESULTS: As 
      of December 2020, a total of 7986 cutaneous events were reported with CDK4/6 
      inhibitors (15% of total AEs with CDK4/6 inhibitors), mainly by consumers 
      (39.6%), with 43.5% classified as serious and 25% requiring discontinuation. In 
      49% of the cases, five or more noncutaneous events were co-reported. The most 
      frequently reported cutaneous events were alopecia (N = 3528), rash (N = 1493), 
      and pruritus (N = 1211): rashes were recorded in the first month (median onset 28 
      days), whereas alopecia and nail alterations were recorded after a median of 67 
      and 112 days, respectively. Several cutaneous AEs were associated with increased 
      reporting, including vitiligo (N = 6; ROR 8.88; 95% CI 2.95-22.46) and bullous 
      dermatitis with ribociclib (N = 7; ROR 2.90; 95% CI 1.13-6.27); erythema 
      multiforme with abemaciclib (N = 9; ROR 5.80; 95% CI 2.57-11.48); onychoclasis (N 
      = 142, ROR 2.27; 95% CI 1.83-2.79) and trichorrhexis (N = 22; ROR 3.27; 95% CI 
      1.78-5.93) with palbociclib. CONCLUSIONS: Although causality cannot be 
      demonstrated, a diverse reporting pattern of cutaneous AEs emerged from FAERS, 
      including dermal/epidermal conditions, hair/nail disorders, and serious bullous 
      conditions, with variable onsets and a remarkable proportion of discontinuations. 
      The potential differential reporting among CDK4/6 inhibitors deserves further 
      investigation.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Raschi, Emanuel
AU  - Raschi E
AUID- ORCID: 0000-0003-0487-7996
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum-University of Bologna, Via Irnerio 48, 40126, Bologna, Italy. 
      emanuel.raschi@unibo.it.
FAU - Fusaroli, Michele
AU  - Fusaroli M
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum-University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
FAU - La Placa, Michelangelo
AU  - La Placa M
AD  - Dermatology Division, Department of Experimental, Diagnostic and Specialty 
      Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy.
FAU - Ardizzoni, Andrea
AU  - Ardizzoni A
AD  - Medical Oncology Unit, Department of Experimental, Diagnostic and Specialty 
      Medicine, Policlinico S. Orsola-Malpighi, Alma Mater Studiorum-University of 
      Bologna, Bologna, Italy.
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Zamagni, Claudio
AU  - Zamagni C
AD  - IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Poluzzi, Elisabetta
AU  - Poluzzi E
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum-University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
FAU - De Ponti, Fabrizio
AU  - De Ponti F
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum-University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
LA  - eng
PT  - Journal Article
DEP - 20211026
PL  - New Zealand
TA  - Am J Clin Dermatol
JT  - American journal of clinical dermatology
JID - 100895290
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
SB  - IM
CIN - Indian J Pharmacol. 2023 May-Jun;55(3):190-191. PMID: 37555416
MH  - *Breast Neoplasms/drug therapy/enzymology
MH  - Cyclin-Dependent Kinase 4/antagonists & inhibitors
MH  - Cyclin-Dependent Kinase 6/antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Odds Ratio
MH  - Pharmacovigilance
MH  - *Protein Kinase Inhibitors
MH  - United States/epidemiology
MH  - United States Food and Drug Administration
EDAT- 2021/10/27 06:00
MHDA- 2022/03/15 06:00
CRDT- 2021/10/26 12:36
PHST- 2021/10/06 00:00 [accepted]
PHST- 2021/10/27 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/10/26 12:36 [entrez]
AID - 10.1007/s40257-021-00645-0 [pii]
AID - 10.1007/s40257-021-00645-0 [doi]
PST - ppublish
SO  - Am J Clin Dermatol. 2022 Mar;23(2):247-255. doi: 10.1007/s40257-021-00645-0. Epub 
      2021 Oct 26.